**7.1 Chemical analysis of EVs**

The chemical analysis of EVs revealed that they contain soluble proteins, lipids, and carbohydrates with immunomodulatory action [79]. Helminthes counter with a palette of protein modulators, from protease inhibitors to receptor ligands that target these pathways [14]. The list of these immunomodulatory molecules are increasing over the last decade [80]. Many parasites release exosome and/or microvesicles. These vesicles play a cornerstone to the downstream communication into the immune system [81]. These vesicles actively induce IL 33 which binds to IL 33R that pledges an allergic reaction. These EVs or exosomes also inhibits activates ILC 2 and eosinophils [77]. Recent investigation on EVs of *H. polygyrus* showed that they suppress receptor for the Alarmin—cytokine IL-33 in ILC 2 [74]. The internalization of EVs causes down regulation of IL 33 and type 1 and type 2 immune cytokines; IL 6 and TNF, and Ym1 and RELMa [81]. Several documents demonstrate that exosomes promote TH 2 slanting towards the activation of DCs and T cells during infection and vaccine development (**Figure 6**) [82]. Recently, evidences are brought forward to the notion that EVs are secreted by both the parasite and the host [80]. Interestingly, it is suggested that there helminth plagiaristic EVs structures could also be used in the inflammation regulation, especially in allergic, autoimmune, and metabolic disorders regulated by miRNA [83, 84]. Helminth immune modulation has some beneficial effects as allergies, and inflammatory and autoimmune diseases which are less common in populations infected with helminthes. A large body of literature provide reasonable evidences on mechanism of immunomodulation that arise from the helminth infections [85].

**167**

**Figure 6.**

*Types of dendritic cells.*

*Goat Immunity to Helminthes*

*DOI: http://dx.doi.org/10.5772/intechopen.91189*

*Goats (Capra) - From Ancient to Modern*

and repress inflammatory processes [73].

**7. Extra-helminthes immune molecules**

to be tightly regulated by one gene product, CCR7. Expression levels of this gene largely control non-migratory and migratory scenarios [43, 71]. In payer patches, CD103, CD11b expressing and non-expressing DCs are well studied that induces lymphocytes [72]. Many T cell receptor (TLR) expressing DCs also induce the production of Immunoglobulin (Ig) A. On the other hand, pDCs can incite IgA directly

Research studies on helminthes immune modulation system is more engrossed to find cytokine activation, release and mechanisms of cytokine-mediated effector functions. This all rely on the first immune recognition, probably PAMPs and DAMPs, and message of early immune response activation or even suppression. Later this signal is converted to sustained and regulatory immune response [14]. It is observed that in the early phase, limited inflammation occurs in the invading tissues which is overlooked by immunoregulatory milieu to evade, and survive [74]. One of the tool these invading parasites is are; (i) apoptotic processes against immune cells [75], (ii) manipulation of Pattern Recognition Receptors (PRRs), (iii) lowering of TH 1/TH 2 cells and (iv) associated cytokines activation [76]. Recently many goat helminthes shown to ubiquitous cog with the release of endocytologic extracellular vesicles (EV) on to cytoplasmic membrane in the intestinal Lamina propria. EVs are vesicles slashed out by different categories of cells which plays role in modulation of immune response to helminthic pathogenesis [77]. Depending on their sizes and origin, these are classified into three types; Microvesicles, Exosomes, and Apoptotic bodies. The exosomes range in size from 30 to 100 nm in diameter that are released by the cells. Microvesicles, however, also called ectosomes—shed 100–1000 nm vesicles or microparticles. Lastly apoptotic

bodies are just 2–4 μm in size that are released by dying cells [78].

The chemical analysis of EVs revealed that they contain soluble proteins, lipids, and carbohydrates with immunomodulatory action [79]. Helminthes counter with a palette of protein modulators, from protease inhibitors to receptor ligands that target these pathways [14]. The list of these immunomodulatory molecules are increasing over the last decade [80]. Many parasites release exosome and/or microvesicles. These vesicles play a cornerstone to the downstream communication into the immune system [81]. These vesicles actively induce IL 33 which binds to IL 33R that pledges an allergic reaction. These EVs or exosomes also inhibits activates ILC 2 and eosinophils [77]. Recent investigation on EVs of *H. polygyrus* showed that they suppress receptor for the Alarmin—cytokine IL-33 in ILC 2 [74]. The internalization of EVs causes down regulation of IL 33 and type 1 and type 2 immune cytokines; IL 6 and TNF, and Ym1 and RELMa [81]. Several documents demonstrate that exosomes promote TH 2 slanting towards the activation of DCs and T cells during infection and vaccine development (**Figure 6**) [82]. Recently, evidences are brought forward to the notion that EVs are secreted by both the parasite and the host [80]. Interestingly, it is suggested that there helminth plagiaristic EVs structures could also be used in the inflammation regulation, especially in allergic, autoimmune, and metabolic disorders regulated by miRNA [83, 84]. Helminth immune modulation has some beneficial effects as allergies, and inflammatory and autoimmune diseases which are less common in populations infected with helminthes. A large body of literature provide reasonable evidences on mechanism of immunomodulation that arise from the helminth infections [85].

**7.1 Chemical analysis of EVs**

**166**

**Figure 6.** *Types of dendritic cells.*

In goats, a definite systematic immune regulations is contemporaneous placed in various world breeds of goats [25]. In sheep, explorative investigates lead us to draw near perfect immune mechanisms followed after the helminth infections and vaccination [86]. It is to remember that helminthes when infect goats, they are not recognize merely whole organism, rather it is a combination of small amino acid sequence derived from PAMPs and DAMPs attached to the cellular peptide-MHC (pMHC) within the groove of MHC molecule [87]. The bound peptide (8–11 amino acids for MHC I and 13–22 amino acid for MHC II) is presented to antigen-presenting cells (APC) through groove—exposed motif (GEM) [45]. The induction of systemic immune responses following parenteral immunization occurs in similar ways in many species including mice, humans, and small ruminants [88].

### **7.2 Mucosal immunity**

The development of effective mucosal immune responses by way of vaccination is considered important because mucosal immunity is able to prevent early establishment of the pathogen and hence could at least theoretically prevent infection at an earlier (less damaging) time point. Thus, vaccines targeting mucosal sites have been in development for a considerable amount of time [88]. The primary protective surface at mucosal sites is the secretion of mucus form gastrointestinal lining. Mucus is a dynamic multimolecular matrix built on polymeric, gel-forming glycoproteins (mucins), with different mucins dominating the barrier at different mucosal sites [89]. At mucosal sites, specialized epithelial cells such as goblet cells secrete gel forming mucins. Upon infection, these cells undergo hyperplasia and increase mucin production, which expands the secreted mucus barrier and provides protection against multiple pathogens [90, 91]. The formation of mucus layer also add on; (a) antimicrobial molecules (e.g., IgA, lysozyme, defensins), (b) immunomodulatory molecules (e.g., cytokines, secretoglobins), (c) repair molecules (e.g., trefoil proteins) [29]. In mice model, the mucin producing Muc 2 are major producer of gel like mucus formation that creates a barrier against contact to the lining in the gastrointestinal tract. This mechanism also provide in return helminthic worms modulating antigen and tolerance [92]. Off the subsets, Muc5ac cells are specifically upregulated after worm infection that also influences expulsion of worm [93, 94]. The sheep model in studying immune mechanisms, with special reference to mucosal immunity, by using nasal vaccines and delivery systems suggested specifically the distribution of the antigen with in the lymph nodes, processing, induction and drainage [88]. Innate lymphoid bundle cells (ILC 2) and TH 2, as discussed above, share common feature of secretion of IL 13 with differential kinetics for each type [29] (**Figure 7**).

### **7.3 T cell subsets**

T cells as well B cells tend to form two major components within the adaptive immune system. The initial T cell development starts in the bone marrow from hematopoietic stem cells (HSCs). The T cell predecessors pass through to the thymus, from where it gets acronym. The differentiation steps provide ultimately culminate into various mature T cell subsets. The whole process is summarized in **Figure 1** [95]. T-cell development/maturation is very much dependent on their presence within the thymus. In mice, absence/removal of it generates severely impaired T cell development [96]. The differentiations and developments of, especially, T cells produces T cells, B cells, natural killer (NK) cells, or dendritic cells (DCs). However, further stoppage within the thymus, further differentiate into these

**169**

**Figure 8.**

**Figure 7.**

*Goat Immunity to Helminthes*

*DOI: http://dx.doi.org/10.5772/intechopen.91189*

*Cell signaling network through mucosal immunity.*

subsets the maturation of these subsets i.e. B cell, NK cell, or DC differentiation

In the formulation of immune response, Treg cells a produce homeostasis and secondly the autoimmune suppression. A growing body of evidence suggests that the Treg cell repertoire contains organ-specific/tissue specific Treg cells. Treg cell share specificities in lymph nodes throughout the body, suggesting that the anatomical distribution of Treg cells is shaped by the presentation of regional organspecific antigens [97]. On the other hand, the Macrophages (Mϕ) show profound differences with various profiles. Under the influence of an alternative phenotype

occurs in bone marrow and fetal liver (Rich eBook).

**7.4 Formulation of immune response**

*Microenvironment in the Helminth infection.*

*Goats (Capra) - From Ancient to Modern*

and small ruminants [88].

**7.2 Mucosal immunity**

In goats, a definite systematic immune regulations is contemporaneous placed in various world breeds of goats [25]. In sheep, explorative investigates lead us to draw near perfect immune mechanisms followed after the helminth infections and vaccination [86]. It is to remember that helminthes when infect goats, they are not recognize merely whole organism, rather it is a combination of small amino acid sequence derived from PAMPs and DAMPs attached to the cellular peptide-MHC (pMHC) within the groove of MHC molecule [87]. The bound peptide (8–11 amino acids for MHC I and 13–22 amino acid for MHC II) is presented to antigen-presenting cells (APC) through groove—exposed motif (GEM) [45]. The induction of systemic immune responses following parenteral immunization occurs in similar ways in many species including mice, humans,

The development of effective mucosal immune responses by way of vaccination is considered important because mucosal immunity is able to prevent early establishment of the pathogen and hence could at least theoretically prevent infection at an earlier (less damaging) time point. Thus, vaccines targeting mucosal sites have been in development for a considerable amount of time [88]. The primary protective surface at mucosal sites is the secretion of mucus form gastrointestinal lining. Mucus is a dynamic multimolecular matrix built on polymeric, gel-forming glycoproteins (mucins), with different mucins dominating the barrier at different mucosal sites [89]. At mucosal sites, specialized epithelial cells such as goblet cells secrete gel forming mucins. Upon infection, these cells undergo hyperplasia and increase mucin production, which expands the secreted mucus barrier and provides protection against multiple pathogens [90, 91]. The formation of mucus layer also add on; (a) antimicrobial molecules (e.g., IgA, lysozyme, defensins), (b) immunomodulatory molecules (e.g., cytokines, secretoglobins), (c) repair molecules (e.g., trefoil proteins) [29]. In mice model, the mucin producing Muc 2 are major producer of gel like mucus formation that creates a barrier against contact to the lining in the gastrointestinal tract. This mechanism also provide in return helminthic worms modulating antigen and tolerance [92]. Off the subsets, Muc5ac cells are specifically upregulated after worm infection that also influences expulsion of worm [93, 94]. The sheep model in studying immune mechanisms, with special reference to mucosal immunity, by using nasal vaccines and delivery systems suggested specifically the distribution of the antigen with in the lymph nodes, processing, induction and drainage [88]. Innate lymphoid bundle cells (ILC 2) and TH 2, as discussed above, share common feature of secretion of IL 13 with differential kinetics for each type

T cells as well B cells tend to form two major components within the adaptive immune system. The initial T cell development starts in the bone marrow from hematopoietic stem cells (HSCs). The T cell predecessors pass through to the thymus, from where it gets acronym. The differentiation steps provide ultimately culminate into various mature T cell subsets. The whole process is summarized in **Figure 1** [95]. T-cell development/maturation is very much dependent on their presence within the thymus. In mice, absence/removal of it generates severely impaired T cell development [96]. The differentiations and developments of, especially, T cells produces T cells, B cells, natural killer (NK) cells, or dendritic cells (DCs). However, further stoppage within the thymus, further differentiate into these

**168**

[29] (**Figure 7**).

**7.3 T cell subsets**

**Figure 7.** *Cell signaling network through mucosal immunity.*

**Figure 8.** *Microenvironment in the Helminth infection.*

subsets the maturation of these subsets i.e. B cell, NK cell, or DC differentiation occurs in bone marrow and fetal liver (Rich eBook).
